3, 5, 5-trimethyloxazolidine-2, 4-dione



Patented Nov. 20, 1951 3,5,5 -TRIMETHYLOXAZOLIDINE-2,4-DIONE Marvin A.Spielman, Waukegan, Ill., assignor to Abbott Laboratories, NorthChicago, 111., a corporation of Illinois No Drawing. Application March2, 1949, Serial No. 79,295

1 Claim. 1 The present invention relates to the chemical compound3,5,5-trimethyloxazolidine 2,4-dione represented by the followingformula:

Etc

The present invention is based upon a research investigation resultingin the discovery that the presence of a methyl group in the 3-positionproduced radical changes in the therapeutic properties of certain5-lower alkyl and 5,5-dilower alkyl oxazolidine-2,4-diones. Withcontinued investigation it was discovered that the N-methyl compoundshaving a lower alkyl group or groups containing from one to three carbonatoms at the 5-position, possess valuable therapeutic properties. It wasdiscovered in particular that of these compounds, the compound3,5,5-trimethyloxazolidine 2,4-dione displayed especially valuabletherapeutic properties.

The basic ring of the compound of the present invention is known in theart as oxazolidine- 2,4-dione. This compound as well as the ,5- dimethylderivative used in preparing the compound of the present invention maybe produced by various processes. For example,5,5-dimethyl-oxazolidine-2,4-dione may be prepared by reacting acetonewith sodium cyanide and with ammonium thiocyanate followed bydesulfurization. This intermediate may also be prepared by condensinga-hydroxyisobutyramide with ethyl chlorocarbonate or by condensing ethyla-hydroxyisobutyrate with urea. Another method described (Traube andAschar (Ben, 46 2,0'77-1913)) consists in the condensation of ethyla-hydroxyisobutyrate with guanidine followed by hydrolysis.

The compound 3,5,5-trimethyloxazolidine-2,4- dione of the presentinvention may be prepared by various processes. The most satisfactoryprocess involves the alkylation of the 5,5-dimethyloxazolidine-2,4-dione intermediate with dimethyl sulfate. The followingexample will serve for illustrative purposes:

ed to about '72 grams of 5,5-dimethyloxazolidine-2,4-dione dissolved in400 cc. of water. To

this solution, with external cooling and violent stirring, are added(dropwise) about 85 grams of dimethyl sulfate, the rate of additionbeing such that the temperature of the reaction solution does not riseabove 50 C. The reaction mixture is then extracted with ether, the etherremoved in the usual manner and the extract distilled at about 82-85 C.at 5 mm. The purifled product crystallized from ethyl ether or fromwater forms stout prisms with a melting point of about -46 C.

The compound of the present invention is characterized b its analgesicproperties coupled with substantially low or relatively no hypnoticactivity. More particularly, the compound has been found to be anexcellent anticonvulsant in the treatment of petit mal epilepsy.

This application is a continuation-in-part of my co-pending applicationSerial No. 779,424, filed October 11, 1947, which in turn is acontinuation-in-part of application Serial No. 630,944, filed November26, 1945, now abandoned, which in turn is a continuation-in-part of myoriginal application Serial No. 403,073, filed July 18, 1941, nowabandoned.

Others may readily adapt the invention for use under various conditionsof service, by employing one or more of the novel features disclosed, orequivalents thereof. As at present advised with respect to the apparentscope of my invention, I desire to claim the following subject matter.

I claim:

The compound 3,5,5-trimethyloxalidine-2;4- dione represented by thefollowing formula:

HaC O MARVIN A. SPIELMAN.

REFERENCES CITED The following references are of record in the file ofthis patent:

Chemical Abstracts, vol. 14, pp. 46 to 48 (1920).

Beilstein, 4th Ed., vol. 27, pp. 251 to 253 (1937).

Groggins, Unit Processes in Organic Synthesis, McGraw-Hill, 2nd. Ed.,pp. 488489 (1938).

